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A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity


Phase 3
18 Years
N/A
Not Enrolling
Both
Colorectal Cancer, Neurotoxicity

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Trial Information

A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity


OBJECTIVES:

- Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent
or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients
receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer.

- Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can
be delivered without chronic neurotoxicity.

- Determine whether CaMg infusions can ameliorate the acute neuropathy associated with
oxaliplatin.

- Determine whether CaMg infusions cause any adverse events.

- Investigate whether CaMg infusions influence quality of life, fatigue, and activities
of daily living of these patients.

- Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced
neurotoxicity.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients
are stratified according to age (< 65 vs > 65), gender, and chemotherapy regimen (FOLFOX4 vs
modified FOLFOX6). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes
immediately before and after each oxaliplatin administration (once every 2 weeks) of
their assigned chemotherapy regimen.

- Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each
oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.

In both arms, treatment continues until chemotherapy is discontinued (approximately 6
months).

Patients complete quality of life questionnaires on day 1, a symptom experience diary on
days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after
completion of study treatment.

Blood samples are collected at baseline and tested for the GSTP1 gene.

After completion of study treatment, patients are followed for at least 3 months.

PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed adenocarcinoma of the colon or rectum

- Stage II disease

- Stage III disease

- Stage IV disease (completely resected with no evidence of residual tumor)

- Must have undergone curative resection for stage II or III disease

- Scheduled to receive 6 months of adjuvant treatment with either of the following
FOLFOX chemotherapy regimens:

- FOLFOX4, comprising leucovorin calcium, fluorouracil, and oxaliplatin (2-week
course)

- Modified FOLFOX6, comprising high-dose leucovorin calcium, high-dose
fluorouracil, and oxaliplatin (2-week course)

PATIENT CHARACTERISTICS:

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL

- WBC ≥ 3,000/mm^3

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Creatinine ≤ 1.5 times ULN

- Calcium normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No pre-existing peripheral neuropathy of any grade

- No hypercalcemia

- No concurrent heart block or a history of heart block

- No other medical condition that, in the opinion of the treating physician, would make
this protocol unreasonably hazardous for the patient

- No family history of a genetic/familial neuropathy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin,
taxanes, or vinca alkaloids

- Concurrent use of bevacizumab or cetuximab in combination with FOLFOX as part of a
clinical trial or clinical practice are allowed

- No concurrent digitalis medication

- No concurrent digoxin

- No concurrent treatment with anticonvulsants such as carbamazepine, phenytoin, or
valproic acid

- No other concurrent neurotropic agents such as gabapentin

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Outcome Measure:

Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event

Outcome Description:

Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)

Outcome Time Frame:

127 days

Safety Issue:

Yes

Principal Investigator

Charles L. Loprinzi, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000471238

NCT ID:

NCT00316914

Start Date:

January 2006

Completion Date:

November 2012

Related Keywords:

  • Colorectal Cancer
  • Neurotoxicity
  • neurotoxicity
  • stage II colon cancer
  • stage III colon cancer
  • adenocarcinoma of the colon
  • stage II rectal cancer
  • stage III rectal cancer
  • stage IV rectal cancer
  • stage IV colon cancer
  • adenocarcinoma of the rectum
  • Colorectal Neoplasms
  • Neurotoxicity Syndromes

Name

Location

CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
Sanford Cancer Center at Sanford USD Medical CenterSioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PCSioux Falls, South Dakota  57105
Avera Cancer InstituteSioux Falls, South Dakota  57105
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Mercy Capitol HospitalDes Moines, Iowa  50307
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Bismarck Cancer CenterBismarck, North Dakota  58501
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501